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Background Hematopoietic Cell Transplant (HCT) is often curative for patients with myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia (AML). However 20-60% of patients relapse post HCT. We aim to identify factors that predict relapse after HCT.
Methods From 2002-2014, 63 pediatric patients underwent HCT for AML or MDS at our institution with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) 22 of whom relapsed. A retrospective review of patients who did or did not relapse was performed comparing clinical variables, chimerism, cytogenetics, flow cytometry and morphology at diagnosis, pre HCT, day 100 post HCT and at relapse.
Results Table 1 describes patient variables. Median time to relapse was D 210 post-HCT (20-1644). Most relapsed early post HCT (54%, 100-365 days p=0.008). Relapse was more frequent in patients receiving RIC versus MAC (50%, 29%, p=0.15) and with matched related donors versus alternative donors (48%, 28%, p=0.2). Both groups were comparable with respect to disease risk, cytogenetics, graft composition, and post HCT complications (>Gr 2 acute graft versus host disease (GVHD), CMV viremia), except for engraftment syndrome which was more frequent in the non relapse group. Relapsed cohort had a higher incidence (63% vs 31%) of partial T-cell chimerism, specifically lower T-cell chimerism at engraftment and D30 (75%, 74.5%) compared to non relapsers (90.5% and 94%), but was not statistically significant (p=0.5 and p=0.3).
Conclusions Relapse is a major cause of mortality in patients that undergo HCT for AML/MDS. Relapse frequently occurred early post HCT, in patients receiving RIC regimens or those with partial donor T cell chimerism at engraftment and D30 post HCT in this small cohort. Further analyses are ongoing to identify a subgroup of patients in whom preemptive intervention is warranted.
| Relapsed (n=22) | Non-relapse (n=41) |
Patient Characteristics |
|
|
Median Age at Transplant (yrs) | 10 | 7.2 |
Gender M F | 12 10 | 29 12 |
Ethnicity Caucasian Hispanic Others | 9 10 3 | 19 12 10 |
De novo AML Secondary AML/MDS | 15 7 | 34 7 |
Risk Stratification High Risk Intermediate Risk Unknown | 13 9 0 | 27 12 2 |
Remission Pre HCT CR1 MDS CR2 Unknown | 14 3 5 0 | 17 9 13 2 |
Transplant Characteristics |
|
|
Median Time to Transplant (days) | 108 (55-492) | 139 ( 16-1349) |
Donor Matched Related Donor Alternative Donor | 11 11 | 12 29 |
Stem Cell Source PBSC BM Cord | 16 5 1 | 24 6 11 |
Conditioning MAC RIC | 13 9 | 32 9 |
GVHD prophylaxis Cyclosporine based Tacrolimus based | 21 1 | 40 1 |
Median cell doses TNC dose (x108/kg) CD34+ dose (x106/kg) MNC dose (x108/kg) CD3 dose (x108/kg) | 7.3 ( 0.95-12.6) 6.0 (2.45-13.0) 5.9 ( 0.14-12.5) 2.3 (0.15-5.8) n=11 | 5.7 (0.34-30.7) 5.9 (0.04-22.5) 2.8 (0.18-11.5) 2.6 (0.27-390) n=16 |
Median Engraftment ANC > 500 Plt > 20K | 13.5 (10-30) 16 (0-36) | 12.5 (6-50) 16 (0-90) |
Mixed T-cell Chimerism | 14 | 13 |
Transplant Complications |
|
|
CMV | 4 | 5 |
aGVHD > grade 2 | 4 | 10 |
cGVHD | 4 | 16 |
Death | 16 | 14 |